Genetic Variation and Genetic Disease Flashcards
what is the genetical difference between two individuals?
0.1% -> accounts to 3 million BP
what does non-coding DNA do / make? (5)
regulatory regions
non-coding RNA genes
centromeres
telomeres
transposons
how often so SNPs occur?
every 1000 bp
what are some disadvantages of genetically diverse species?
new genetic mutations can lead to disease that are not compaitble with environment
some mutations can be deletarious but same time offer protection to other diseases (SCT)
where are most genetic differences located in the genome - where do you find regions of low and high genetic variation?
regions of low genetic variation tend to be in conserved regions -> have really important functions
regions of high genetic variation tend to be in areas of DNA replication errors occur (e.g. lots of repeat sequences)
how many genes? how many are hetero and homo?
how many of mutations are silent?
whats the balance of new to previously inherited variation?
~ 21 000 genes
~ 13 000 heterozygous
~ 9 000 homozygous
- about half of homo and hetero variants are silent and half affect
- most variants are passed on from parents BUT do get some novel variants
what are variants called that occur at a frequency >1%?
polymorphism
what are copy number variations?
A copy number variation (CNV) is when the number of copies of a particular gene varies from one individual to the next.
(Following the completion of the Human Genome Project, it became apparent that the genome experiences gains and losses of genetic material. The extent to which copy number variation contributes to human disease is not yet known. It has long been recognized that some cancers are associated with elevated copy numbers of particular genes)
very rare, but high size affect are generally what type of diseases?
vary rare but high: normally mendelian / mongenic diseases (e.g. CF / HD)
how do we detect genetic variation?
- PCR (polymerase chain reaction)
- sequencing
- next generation sequencing
what is PCR used for?
how does PCR work?
PCR: amplifies a region of interest within the human genome, using a template DNA and specific primers
- denaturation: heats DNA to over 90 degrees - opens DNA up
- annealing: 54 degrees. primer is added. DNA binds to primers
- extension: 72 degrees. add polymerase enzymes. builds DNA
repeat x lots
what is sanger sequencing?
(golden standard for genetic testing)
(Sanger sequencing is the process of selective incorporation of chain-terminating dideoxynucleotides by DNA polymerase during in vitro DNA replication)
uses dideoxyribonucleic acids (ddNTP) to terminate polymerization reaction of DNA.
can find every single base pair in a sequence!
what is next generation sequencing? what are the different types?
future of genetic analysis. different types:
- whole genome sequencing
- whole exome sequencing - sequencing all exons in genome (~2% of genome). no info on mutations outside of exons.
RNA sequencing (RNAseq) - sequencing all expressed RNA and expression analysis. (RNA is direct result of exons to RNA, but also RNAseq gives info about which genes are expressed and if highly / lowly expressed).
what type of info does NGS give?
what do you need for NGS to be useful?
- generates terabytes worth of info. need sensible biological interpreation and good bioinformatics
- need a reference genome to compare NGS data to
why use NGS?
great for discovering new genes that cause rare inherited diseases:
a) <5% of the population
b) 7000 rare disordes - often disabling
c) 85% have a single gene defect
d) early knowledge may avoid disablity / give better clinical care
why is molecular diagnosis and targeted therapy good?
what can it be used for? (x4)
good: offers personalised approach to care. can tailor to specific genetic conditions of patient
- selection of embryos prior to implantation in IVF (carry out genetic testing on embryos and screen for mutations)
- personalised chemotherapy (take a biopsy of cancer and sequence DNA. if have specific changes to target molecules, can target those molecules with chemo. e.g. herceptin)
- gene therapy for genetic conditions (v experimental)
- pharmacogenomics
what is pharmacogenomics? and what is idea behind it?
we all react differently to drugs due to variation in:
- absorption
- distribution
- metabolism
- elimination
- variability of target receptors
SO knowing these changes, you can tailor doses to specific person
what are ethical considerations need with genetic testing?
- what do results actually mean?
- proper genetic counselling available?
- data protection (insurance companies)
- post screening abortion? should it be?
- should embryos be screened prior to implementation?
- how predictive are the tests? BRAC2 mutations can occur -> increased risk yes, but not 100% will get it
- is there even a cure for the disease?
